Survival rates for oral cancer patients have remained unchanged in the past several decades largely because of the late identification of the disease and the high rate of local recurrence after treatment. We have used the unique medical infrastructure in British Columbia to establish one of the largest cohort studies of dysplasia and cancer patients worldwide in order to systematically follow changes in clinical and pathological parameters, to evaluate established microsatellite markers for prognostic significance alone and in combination with these features, and to develop new genetic tools for risk prediction using genomic profiles generated from samples collected from the study. As yet, little research has been done on alternate approaches that would use different technology in conjunction with these molecular approaches to create an integrated plan for patient assessment and management that would be rapid and cost-effective. This proposal will evaluate 3 innovative, potentially complementary visualization and imaging devices (the VELScope, the ClearCyte and the Getafics, alone and in combination, for early detection and follow-up of oral premalignant lesions (OPLs) and oral cancer. The VELScope is a direct visualization device which makes use of tissue autofluorescence to detect and delineate abnormal lesions. The ClearCyte and Getafics are quantitative imaging microscopy systems. The ClearCyte is a fully automated imaging cytometry system which can automatically scan an entire slide and collect images and data from all the cells present. Getafics is a semi-automated imaging microscopy workstation which collects images of sectioned material and analyzes individual cell nuclei and their spatial arrangement within the tissue imaged. The proposed study will use patients enrolled in the ongoing longitudinal study as well as a cohort accrued from a highrisk community clinic. The study will: 1) Determine the prevalence of alterations detected by the devices as well as sensitivity/specificity for high-grade OPLs and cancer (Study Aim 1);2) Determine the relationship between characteristics observed with these devices at first assessment and throughout follow-up with the development of adverse outcomes (progression or recurrence) (Study Aim 3);and 3) Determine whether the integration of these devices with molecular tests and clinicopathological features will facilitate the identification of critical changes earlier and with greater specificity (Study Aim 3). This information will be used to guide the identification and risk assessment of community patients and their triage to regional and cancer hospitals in a Province-wide clinical network being established by the British Columbia Oral Cancer Prevention Program in BC.